Testing Could Reduce Episodes of Dangerous Bleeding in People Who Take the Blood Thinner

Three medical-safety experts say the blood thinner Pradaxa can cause dangerous bleeding episodes that could often be avoided by giving patients blood tests to assess how their bodies respond to the drug.

The researchers, in a British Medical Journal article to be published Wednesday, are from the Institute for Safe Medication Practices in Pennsylvania and the University of Ottawa in Canada. They write that levels of Pradaxa in the blood of patients can vary more than fivefold, and that these amounts are linked to potentially fatal bleeding.

Pradaxa, generically called dabigatran, was approved by the U.S. Food and Drug Administration in October 2010 without a requirement that blood levels be monitored. The drug was approved for use in patients prone to having strokes from a faulty heartbeat called atrial fibrillation, or A-fib.

The ability to prescribe Pradaxa without requiring regular blood tests is one of the chief selling points of the drug, which generated $837 million in U.S. sales in 2013, according to data provider
IMS Health.
By contrast, warfarin, the decades-old blood thinner that is far less costly, does require patients to get blood tests.

Pradaxa marketing materials from its maker, Boehringer Ingelheim GmbH of Germany, specifically point out that warfarin "requires regular blood tests…to see if your blood-thinning level is in the right range." Warfarin patients also need to pay attention to the amount they eat of certain foods, such as some leafy green vegetables, which can affect the level of warfarin in the blood. With Pradaxa, company materials say, there is "no need for regular blood tests" and there are "no dietary restrictions."

The company disputed the BMJ findings, saying it has "made a robust effort to find ways to utilize plasma levels to further improve the risk/benefit profile of Pradaxa…The truth is the totality of scientific evidence does not support dosing decisions for Pradaxa based on blood levels."

It said it is "concerned that this publication may alarm patients and prompt them to stop taking Pradaxa, thereby increasing their risk of stroke."

FDA officials declined to comment. In May, the agency said it had studied 134,000 Medicare patients and found that Pradaxa was linked to a lower risk of strokes, brain bleeds and death than warfarin. But, the agency said, Pradaxa was linked to a higher risk of major gastrointestinal bleeding compared with warfarin.

In a recent perspective piece, an FDA senior official, Dr. Ellis Unger, said that Pradaxa is "superior" to warfarin in avoiding strokes and that "most of the bleeding" with Pradaxa and similar new drugs "is not serious." An FDA perspective piece features observations based largely on data the agency has analyzed.

In Wednesday's British Medical Journal article, Thomas J. Moore, Michael R. Cohen and Donald R. Mattison write that a fixed dose of dabigatran "had wide variability in plasma levels that were directly related to the risk of bleeding." They estimate that there was a 5.5-fold variability in the blood levels of those on the drug.

"Regulators should recommend plasma level testing in all new patients, and eliminate the recommendation dabigatran does not in general require routine anticoagulant monitoring," the authors write.

They also contend the FDA should approve a lower dose of Pradaxa than is currently available. Such a lower dose, they write, "could reduce serious bleeding without loss of efficacy in preventing strokes."

In a separate editorial in the same publication, Drs. Blake Charlton and Rita Redberg of the University of California San Francisco write that "the risks of dabigatran could be larger than previously reported."

"Litigation revealed internal documentation that the company failed to disclose that monitoring might reduce risk of stroke and bleeding," Drs. Charlton and Redberg write.